Tag: 5/3/21

Categories : Cancer Metabolic DisordersTags :

‘Obesity Paradox’ in Kidney Cancer Continues to Mystify

On By ModernMedia

Obese patients with metastatic renal cell carcinoma (RCC) were more likely to survive compared to their normal weight counterparts when receiving immune checkpoint inhibitors (ICI), a study has shown.

RCC is the most deadly of the urogenital cancers, and its incidence is increasing. Males are twice as likely as females to develop it.
A team of researchers including Toni Choueiri, MD, of Dana-Farber Cancer Institute in Boston, conducted an analysis of 735 metastatic RCC patients who received PD-1/L1 immunotherapies. 

Those with a BMI of 25 or greater had significantly longer overall survival (OS), with 1-year rates of 79% versus 66% for those with a BMI below that cutoff. This relationship was observed across tumour categories.

“These findings are consistent with the obesity paradox that was previously seen during the VEGF-targeted therapy era,” the team noted.

“Several hypotheses have attempted to explain this clinical observation in RCC,” Choueiri’s team wrote. “Low fatty acid synthase gene expression, which is inversely correlated with BMI, was associated with longer OS in VEGF-treated patients. Transcriptomic analysis suggests that patients with obesity have tumors with increased angiogenesis gene signatures and peritumoral adipose tissues with increased hypoxia, inflammation, and immune cell infiltration signatures.”

In 319 patients with next-generation sequencing technology, there was no difference between groups for tumour mutation burden, at an average 6.8 mutations per megabase for the low and high BMI groups. Genomic alteration frequency analysis also picked up no differences.

Limitations of the study authors included its retrospective nature, incomplete gene-expression profiling, and between-group imbalances. Patients with higher BMI had greater odds of having better performance status and being in more favourable risk groups, had greater odds of having clear cell histology, having had prior nephrectomy, and having received a checkpoint inhibitor as first-line therapy.

Source: MedPage Today

Journal information: AKA Lalani, et al “Assessment of immune checkpoint inhibitors and genomic alterations by body mass index in advanced renal cell carcinoma” JAMA Oncol 2021; DOI: 10.1001/jamaoncol.2021.0019.

Categories : Gender GeneticsTags :

Health Conditions Driven By Evolution and Genetic Sex Differences

On By ModernMedia

A new study shows that the human genome has been subject to selection pressures favouring different characteristics in females and males, which makes males more susceptible to a variety of health conditions.

Genetic sex differences have long been known to have an impact on health. On balance, while females have certain conditions unique to them (eg, cervical cancer), or are more prone to (eg, multiple sclerosis), males are more prone to certain medical conditions, bringing down their average life expectancy compared to women.

Their research adds to a body of knowledge on genomic influences on health, which can map hereditary traits onto individuals and populations to guide healthcare. Looking at health conditions through the lens of genomics can help clinicians to better understand them and guide development of new treatments.  

“Our cells have memories and they carry the accumulation of all the changes our ancestors have experienced over millions of years,” said Rama Singh, a McMaster biology professor who wrote the paper with his son, Karun Singh, an associate professor of neuropathology at the University of Toronto, and Shiva Singh (no relation), a biology professor at Western University.

The researchers focussed on autism, which is a good example of the way men and women develop medical conditions differently; though they inherit the same sets of genes from the parents, the expression of those genes differs greatly by sex.

Though human behaviour regarding mate selection has changed, those genetic characteristics remain and continue to be expressed in the health and development of modern men.

The male genome has been shaped over millions of years, and favours reproduction in the early years of male maturity to pass on genes, at the expense of genetic well-being in the long term.

Women are less vulnerable to most health conditions, living longer than men because their genomes have evolved to protect against unhealthy traits in the male genome, resulting in better immunity and more longevity.

The same forces shaping human selection also apply to mental health, even though it is complex. Women are more prone to anxiety and depression, while men are more prone to anti-social disorders.

“If women and men were any more different, they would be different species,” joked corresponding author, Prof Karun Singh.

Male-female imbalance is especially pronounced in autism, with being up to four times more likely to have some form of autism, and are also more likely to have severe symptoms. Evolution has resulted in a higher threshold, protecting females from developing the condition.

Although autism is not solely the result of inherited characteristics, it does appear that boys are more likely to develop it as a result of other inhertied characteristics rendering them more vulnerable to environmental, developmental and other factors that give rise to autism.

“One of the reasons I think this is interesting is that it offers a perspective that is not well represented in the medical literature. This is a really good example of the perspective that geneticists and evolutionary biologists can add to health research,” said Prof Karun Singh.

Source: News-Medical.Net

Journal information: Singh, R. S., et al. (2021) Origin of Sex-Biased Mental Disorders: An Evolutionary Perspective. Journal of Molecular Evolution. doi.org/10.1007/s00239-021-09999-9.

Categories : COVIDTags :

Bolsonaro Tells Brazilians to ‘Stop Whining’ About COVID

On By ModernMedia

Amidst a surge of COVID cases and deaths in Brazil that have brought its healthcare system to the brink of collapse, President Jair Bolsonaro has told its citizens to “stop whining”, saying that the country must balance economic concerns against controlling the pandemic.

According to Brazil’s health ministry, the country has suffered 260 000 deaths from the virus, the second highest in the world after the United States.

“Stop whining. How long are you going to keep crying about it?” Mr Bolsonaro said at an event. “How much longer will you stay at home and close everything? No one can stand it anymore. We regret the deaths, again, but we need a solution.”

In order to stave off further disaster, a number of local governments have started taking matters into their own hands by imposing their own curfews and other social distancing measures. 

São Paulo’s governor, João Doria, who has been particularly critical of Mr Bolsonaro’s response to the pandemic, called President Bolsonaro “a crazy guy” for attacking “governors and mayors who want to buy vaccines and help the country to end this pandemic”.

“How can we face the problem, seeing people die every day? The health system in Brazil is on the verge of collapse,” Mr Doria said.

This comes as a Duke University scientist, another Bolsonaro critic, warned of the danger of another quarter of a million deaths, and called for an immediate lockdown to help control the situation.

The situation is exacerbated by the emergence of the P.1 variant which emerged in Manaus, and has high transmissibility and the capability to evade immunity, having a 25% to 60% chance of reinfecting an immune individual.

Source: BBC News

Categories : COVID General Interest UncategorizedTags :

Nurse Recounts His Year on the Frontlines

On By ModernMedia
Stethoscope. Photo by Robert Ruggiero on Unsplash

One year into the first case of COVID being detected in South Africa, one nurse recounts the hardships he and other healthcare workers have faced as they battled against the pandemic.

Lebohang Nkoana, a nurse on the frontline at Thelle Mogoerane Hospital in Vosloorus, Ekurhuleni, spoke to IOL of his experiences.

“When Covid-19 came, no one knew what to expect,” said Nkoana, who has been a nurse for eight years and is also a branch secretary for the Democratic Nurses Organisation of SA.

“It was devastating because we were already short-staffed. At first, we were resistant. We did not want to work with Covid-19 patients

“We were just using normal non-sterile gloves. Then we stopped working for two days as we did not want to risk our lives and also because we were not fully informed about the disease.”

Like many in the first days of the pandemic, he was forced to work without adequate PPE. Lack of regulation and price gouging had also worsened the PPE situation during the early days of the pandemic.

“There was no PPE, no increment, nothing. I had to use what I had at my disposal to protect myself and render a service.

“I went into a Covid ward to save lives, but in the process, exposed myself.”

Mr Koana contracted COVID during the course of his duty, and lost 19 of his colleagues to the disease, with little in the way of support for his trauma. He is also stigmatised in his community, as people assume that he has COVID. He also fears for his wife and two children.

“I am not scared for myself, because as a nurse, I took an oath. I am scared for my children. If I bring the virus home and it kills my wife, who will take care of our children?”

Source: IOL

Categories : COVIDTags :

Clinical Trial for Ivermectin Delivers Disappointing Results

On By ModernMedia

A randomised clinical trial in Colombia for ivermectin treatment in mild COVID returned disappointing results.

An anti-parasitic normally used for livestock, ivermectin has gathered considerable attention as a possible COVID treatment in recent months, especially locally, with stocks containing the product depleted in the last month. There are no ivermectin-containing products in South Africa for human use. The South African Health Products Regulatory Authority is of the view that the evidence for ivermectin is currently inconclusive.

“To our knowledge, preliminary reports of other randomized trials of ivermectin as treatment for COVID-19 with positive results have not yet been published in peer-reviewed journals,” the researchers wrote.

  The randomised, double-blind, single-center study took place from July 15 to December 21, 2020. Patients were assigned to either receive an oral dose of 300 μg/kg of body weight per day of ivermectin or placebo, for five days. Follow-up took place on days 2, 5, 8, 11, 15, and 21. The primary trial outcome was resolution of symptoms within 21 days.  

However, the study was not without its share of problems. The initial primary outcome was time from randomisation until worsening of symptoms by two points on an ordinal scale, but few patients reached this endpoint in the expected time. This meant the sample size needed to maintain sufficient power was “unattainable.” To accommodate this, the primary endpoint was changed to time from randomisation to symptom resolution by day 21, retaining the original sample size.

To make matters worse, a labelling error occurred, where ivermectin was mistakenly given to all patients from September 29 to October 15, so the protocol was amended, with these patients excluded from the primary analysis. The researchers then recruited more patients to retain the originally calculated study power.

Despite these problems, the researchers said the findings remained valid within the confines of its other limitations. Limitations to the study, the researchers said, included that it was not conducted or completed according to the original design; that it may have been underpowered to detect a smaller, clinically meaningful reduction in the primary endpoint; and virological assessments were not included, only clinical characteristics.

Larger trials would be needed “to understand the effects of ivermectin on other clinically relevant outcomes,” concluded the researchers.

Source: MedPage Today

Journal information: López-Medina E, et al “Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19 — A Randomized Clinical Trial” JAMA 2021; DOI: 10.1001/jama.2031.3071.

Categories : Mental Health New Compounds and TreatmentsTags :

Neurocrine’s Anticipated Schizophrenia Drug Flops in Clinical Trial

On By ModernMedia

Pharmaeceutical company Neurocrine’s anticipated schizophrenia drug, luvadaxistat, failed to have an impact on negative symptoms in a key clinical trial, but still showed promising cognitive benefits.

Neurocrine Biosciences had licensed seven of Takeda’s psychiatry drugs last year for over $2 billion. Luvadaxistat was the furthest along, having entered Phase 2 testing in 2017.

The experimental drug is supposed to help schizophrenia patients cope with “negative symptoms”—a range of difficult-to-treat conditions such as lack of motivation, trouble communicating and limited emotion. The drug is designed to block an enzyme that degrades a certain kind of amino acid important for brain function.

However, according to results from a mid-stage study, in comparison to placebo, patients treated with the drug didn’t perform significantly better, as measured by a scale that assesses the severity of negative symptoms.

While there was excitement around the science behind luvadaxistat, Wall Street analysts lost much of their optimism in the programme last month, after Concert Pharmaceuticals halted development of CTP-692, an experimental drug based on the same mechanism, after trials also saw disappointing results. 

Nevertheless, there remains a path ahead for luvadaxistat as Neurocrine is setting up to analyse the drug’s efficacy for cognitive benefits, as it appears that these results at least were in line with scientific predictions.

Source: BioPharma Dive